The long-term objective is to uncover the biological function of ergothioneine, a thiolimidazole betaine which is present in mammalian tissues, plants, and microorganisms, with the hope that we can gain an appreciation of varying levels in human tissues to normal and abnormal metabolic processes. A systematic study of ergothioneine biosynthesis in Neurospora is being pursued in the expectation that knowledge of the factors controlling synthesis may help to establish function. The novel pathway of biosynthesis via an intermediate sulfoxide and requiring molecular oxygen will be exploited by investigating the possibility that ergothioneine function is related to metabolic reactions concerned with the utilization of oxygen, and may be involved with oxygen toxicity and enzymes such as superoxide dismutase, catalase, or peroxidase. We also wish to explore the possibility that the sulfoxide has a biological function, such as an inhibitor of free radical chain reactions. Other studies will be concerned with the possible function of ergothioneine as a protective agent against UV radiation damage to nucleic acids, and as a possible effector for various isolated enzyme systems.